Neurophysiology of gastrointestinal pain

The only non-general sensation that can be evoked from the gastrointestinal (GI) tract is that of pain ranging from mild discomfort to intense pain. However, in certain regions of the gut, such as the rectum and gastro-oesophagus, the feeling of pain can be preceded by non-painful sensations of distension at lower stimulus intensities. GI pain is often dull, aching, ill-defined and badly localized. In some cases, GI pain is projected to areas of the body away from the originating viscus ('referred' pain). These properties indicate that the representation of internal organs within the central nervous system is very imprecise. Behavioural, neurophysiological and clinical evidence shows that most forms of GI pain are mediated by activity in visceral afferent fibres running in sympathetic nerves and that the afferent innervation of the gut mediated by parasympathetic nerves is not primarily concerned with the signalling and transmission of GI pain. As for the encoding mechanism of the peripheral sensory receptor in the gut, there is evidence for the existence of specific visceral nociceptors in some locations (e.g. the biliary system) and for the existence of non-specific 'intensity' type receptors in other locations (e.g. the colon). In any case, the actual number of nociceptive afferent fibres in the gut is very small and this explains why large areas of the GI tract appear to be insensitive or require considerable stimulation before giving rise to painful sensations. The few nociceptive afferents contained in sympathetic nerves can excite many second order neurones in the spinal cord which in turn generate extensive divergence within the spinal cord and brain stem, sometimes involving long supraspinal loops. Such a divergent input can activate many different systems, motor and autonomic as well as sensory, and thus trigger the general reactions that are characteristic of visceral nociception: a diffuse and ill-localized pain sometimes referred to somatic areas, and autonomic and somatic reflexes that result in prolonged motor activity.     

Cardiac Pain, Sympathetic Afferents, and Life-Threatening Arrhythmias

Cardiac Pain, Sympathetic Afferents, and Life-Threatening Arrhythmias. Myocardial ischemia activates receptors of sympathetic and vagal afferent fibers. Although both afferent pathways are excited, this article primarily focuses on the sympathetic pathways. Increased sympathetic afferent activity to cells of the spinal cord can lead to cardiac pain and reflex sympathetic hyperactivity that can be quite arrhythmogenic. Complicating factors that affect the relationship arises from activation of vagal afferent fibers. Sympathetic afferent fibers in the ventricle appear to be composed of mechanosensitive and chemosensitive receptors. Sympathetic afferent fibers excite cells of origin of the spinothalamic tract, the classical pain pathway that transmits information about noxious somatic and visceral episodes to areas of the brain involved with pain perception. Activation of selected brainstem nuclei, the vagus, and the dorsal columns can suppress afferent information from the heart that excites spinothalamic tract cells. Excitation of sympathetic afferent fibers initiates a series of cardiovascular reflexes, some of which may affect cardiac electrical stability significantly. Increased arrhythmogenesis can be reduced when C₈-T₅ dorsal roots are transected. Stimulation of cardiac nerves that involve the left stellate ganglion can produce life-threatening arrhythmias, particularly if combined with myocardial ischemia or infarction. Through reflex mechanisms, activation of sympathetic afferent fibers can suppress activity of vagal efferent fibers. If prevention of cardiac pain through reduced firing or inhibition of cells in the spinothalamic tract reduces afferent sympathetic activity that occurs during acute myocardial ischemia, it would be logical to surmise that another significant benefit would follow, namely reduced risk for malignant arrhythmias.     

Brain responses to visceral and somatic stimuli in patients with irritable bowel syndrome with and without fibromyalgia

OBJECTIVE: Symptoms of irritable bowel syndrome (IBS) and fibromyalgia (FM) commonly coexist. We hypothesized that one of the mechanisms underlying this comorbidity is increased activation of brain regions concerned with the processing and modulation of visceral and somatic afferent information, in particular subregions of the anterior cingulate cortex (ACC). METHODS: Regional cerebral blood flow (rCBF) was assessed in age-matched female IBS (n = 10) and IBS + FM (n = 10) subjects using H(2)(15)O positron emission tomography during noxious visceral (rectal) and somatic pressure stimuli. RESULTS: GI symptom severity was significantly higher in the IBS patients compared with the IBS + FM patients (p < 0.05). In addition, IBS + FM patients rated somatic pain as more intense than their abdominal pain (p < 0.05). Whereas the somatic stimulus was less unpleasant than the visceral stimulus for IBS patients without FM, the somatic and visceral stimuli were equally unpleasant in the IBS + FM group. Group differences in regional brain activation were entirely within the middle subregion of the ACC. There was a greater rCBF increase in response to noxious visceral stimuli in IBS patients and to somatic stimuli in IBS + FM patients. CONCLUSION: Chronic stimulus-specific enhancement of ACC responses to sensory stimuli in both syndromes may be associated with cognitive enhancement of either visceral (IBS) or somatic (IBS + FM) sensory input and may play a key pathophysiologic role in these chronic pain syndromes.     

Pain without nociception?

We describe a young woman with complete cervical spinal cord transsection, who developed significant abdominal pain, triggered by gastric distension and deep abdominal palpation. On the basis of the nature of her spinal cord injury, her brain-gut axis was limited to vagal pathways. Studies in mammalian models of human visceral sensation consistently showed that the subdiaphragmatic vagus contains a homogeneous population of afferents that are activated by low-intensity stimuli, which are generally believed to be important in regulating autonomic function and perhaps contributing to visceral sensory experiences triggered by such low-intensity stimuli (e.g. fullness, nausea), but not pain, although many fibers encode stimuli well into the noxious range. In contrast, spinal afferent pathways include fibers with high-activation thresholds that are thought to represent specialized nociceptors. This illustrative case argues against an exclusive role of specialized nociceptive pathways in visceral pain, but supports a concept of intensity coding with the composite of vagal and spinal input contributing to conscious perception and pain.     

Rectal sensory perception in females with obstructed defecation

PURPOSE: Parasympathetic afferent nerves are thought to mediate rectal filling sensations. The role of sympathetic afferent nerves in the mediation of these sensations is unclear. Sympathetic nerves have been reported to mediate nonspecific sensations in the pelvis or lower abdomen in patients with blocked parasympathetic afferent supply. It has been reported that the parasympathetic afferent nerves are stimulated by both slow ramp (cumulative) and fast phasic (intermittent) distention of the rectum, whereas the sympathetic afferent nerves are only stimulated by fast phasic distention. Therefore, it might be useful to use the two distention protocols to differentiate between a parasympathetic and sympathetic afferent deficit. METHODS: Sixty control subjects (9 males; median age, 48 (range, 20–70) years) and 100 female patients (median age, 50 (range, 18–75) years) with obstructed defecation entered the study. Rectal sensory perception was assessed with an infinitely compliant polyethylene bag and a computer-controlled air-injection system. This bag was inserted into the rectum and inflated with air to selected pressure levels according to two different distention protocols (fast phasic and slow ramp). The distending pressures needed to evoke rectal filling sensations, first sensation of content in the rectum, and earliest urge to defecate were noted, as was the maximum tolerable volume. RESULTS: In all control subjects, rectal filling sensations could be evoked. Twenty-one patients (21 percent) experienced no sensation at all in the pressure range between 0 and 65 mmHg during either slow ramp or fast phasic distention. The pressure thresholds for first sensation, earliest urge to defecate, and maximum tolerable volume were significantly higher in patients with obstructed defecation (P<0.001). In each subject, the pressure thresholds for first sensation, earliest urge to defecate, and maximum tolerable volume were always the same, regardless of the type of distention. CONCLUSION: Rectal sensory perception is blunted or absent in the majority of patients with obstructed defecation. The observation that this abnormality can be detected by both distention protocols suggests that the parasympathetic afferent nerves are deficient. Because none of the patients experienced a nonspecific sensation in the pelvis or lower abdomen during fast phasic distention, it might be suggested that the sympathetic afferents are also deficient. This finding implies that it is not worthwhile to use different distention protocols in patients with obstructed defecation.     

Capsaicin sensitive-sensory nerves and blood pressure regulation

Capsaicin (8-methyl-N-vannillyl-6-nonenamide), via binding to the vanilloid receptor subtype 1 (VR1), stimulates a subpopulation of primary afferent neurons that project to cardiovascular and renal tissues. These capsaicin-sensitive primary afferent neurons are not only involved in the perception of somatic and visceral pain, but also have a "sensory-effector" function. Regarding the latter, these neurons release stored neuropeptides through a calcium-dependent mechanism via the binding of capsaicin to the VR1. A subset of capsaicin-sensitive sensory nerves contains calcitonin gene-related peptide (CGRP) and substance P (SP). These sensory neuropeptides are potent vasodilators and natriuretic/diuretic factors. Neonatal degeneration of capsaicin-sensitive sensory nerves has revealed novel mechanisms that underlie increased salt sensitivity and several experimental models of hypertension. These mechanisms are reviewed, which include insufficient suppression of plasma renin activity and plasma aldosterone levels subsequent to salt loading, enhancement of sympathoexcitatory response in the face of a salt challenge, activation of the endothelin-1 receptor, and impaired natriuretic response to salt loading in capsaicin-pretreated rats. These data indicate that sensory nerves counterbalance the prohypertensive effects of several neuro-hormonal systems to maintain normal blood pressure when challenged with salt loading. Mechanisms underlying pneumotoxicity and pulmonary hypertension as revealed by degeneration of capsaicin-sensitive nerves are also discussed. Finally, the therapeutic utilities of capsaicin, endogenous anandamide, and CGRP agonists are assessed.     

Role of visceral afferent mechanisms in functional bowel disorders

This report analyzes the clinical and physiological evidence supporting a role for altered visceral afferent mechanisms in the pathogenesis of two functional bowel syndromes: noncardiac chest pain and the irritable bowel syndrome. Considerable recent evidence indicates that increased contractility is present only in a minority of patients and that hypercontractile episodes are not temporally related to abdominal pain. In contrast, altered sensation and motor reflexes in response to physiological stimuli, such as mechanical distention or acid, is common when appropriately investigated. The vagal and spinal afferent innervation mediates visceral sensation and is involved in multiple reflex loops regulating gastrointestinal effector function, such as motility and secretion. Sensory input can be modulated peripherally at the afferent nerve terminal, at the level of prevertebral ganglia, the spinal cord, and the brainstem. An up-regulation of afferent mechanisms would result both in altered conscious perception of physiological stimuli and in altered motor reflexes. Current evidence is consistent with an alteration in the peripheral functioning of visceral afferents and/or in the central processing of afferent information in the etiology of altered somatovisceral sensation and motor function observed in patients with functional bowel disease.     

Sustained decreased in coronary blood flow and excitation of cardiac sensory fibers following sympathetic stimulation.

The effect of electrical stimulation of the efferent cardiac sympathetic nerves on activity of afferent cardiac fibers in the sympathetic nerves and coronary hemodynamics of anesthetized dogs has been examined. During partial constriction of the coronary artery, a brief stimulation of the efferent cardiac sympathetic nerves resulted in sustained excitation of the afferent fibers and a sustained decrease in blood flow of the constricted artery which were associated with systolic bulge of the left ventricle and elevation of the ST segment of electrocardiogram. These changes were not produced without constriction. Pretreatment with phentolamine suppressed excitation of the afferent fibers, development of systolic bulge and elevation of the ST segment. Also, the decrease in coronary blood flow induced by stimulation was replaced by an increase after the administration of the agent. Propranolol suppressed excitation of the fibers, systolic bulge and elevation of the ST segment, but could not eliminate the decrease in blood flow. The results indicate that sympathetic stimulation caused a decrease in coronary blood flow through excitation of the alpha-adrenergic receptors while increasing cardiac work load and energy requirements through excitation of the beta-adrenergic receptors, leading to more severe myocardial ischemia and excitation of the afferent fibers.     

Prevertebral ganglia and intestinofugal afferent neurones

Intestinofugal afferent neurones (IFANs) are a unique subset of myenteric ganglion neurones that regulate normal gastrointestinal function. The IFANs relaying mechanosensory information to sympathetic neurones of the prevertebral ganglion (PVG) function as volume detectors. It is possible that mechanosensory information arriving in the PVG via axon collaterals of visceral spinal afferent nerves can be modulated entirely within the PVG itself.     

肠道炎症诱导的内脏和躯体痛觉过敏

背景：慢性腹痛是功能性胃肠病患者常见症状之一,此类患者亦可同时具有较明显的躯体症状。内脏和躯体症状并存极大影响了患者的生活质量,并增加就医负担。目的：观察肠道炎症后大鼠内脏和躯体痛觉,探究两者间的联系和可能的共同发病机制。方法：80只雄性Sprague—Dawley大鼠随机分为模型组、溶剂对照组和阴性对照组,分别给予20mgTNBS／乙醇混合液、50％乙醇和0．9％NaCl溶液灌肠。灌肠8周后,行不同压力结直肠扩张（CRD）诱导内脏运动反射（VMR）以评估大鼠内脏痛觉。以机械缩足反射阈值（MWT）和甩尾反射潜伏期（TFL）评估躯体痛觉。结果：造模8周后模型组大鼠结肠黏膜病理表现与两组对照组相比无明显差异,未见明显溃疡和炎性细胞浸润。与两组对照组相比,32．5％的模型组大鼠内脏痛觉阈值明显下降（P〈0．001）,且这部分内脏痛觉高敏感的模型组大鼠MWT和TFL均明显降低（P〈0．001）。结论：本研究建立的动物模型模拟了感染后肠易激综合征状态,TNBS诱导的肠道炎症同时导致了大鼠内脏和躯体痛觉过敏,有助于进一步探究内脏和躯体痛觉过敏的共同发病机制。     

Experimental study on the changes of blood pressure induced by afferent stimulation on the somatic nerves (author's transl)]

It has been shown by many authors that afferent stimulation of various somatic nerves results in the different types of responses with regard to blood pressure and heart rate. It was revealed by Hunt that afferent "weak" stimulation of the somatic nerves caused depressor responses, and "strong" stimulation, pressor responses. Ranson and Gordon thought that the depressor response to the afferent stimulation of the somatic nerves would involve the thick myelinated nerve fibers, and the pressor response, the fine non-myelinated nerve fibers. On the other hand, it has been postulated that the socalled chest pain and/or nonspecific complaints observed in patients with myocardial infarction, angina pectoris and neurocirculatory asthenia (NCA) are related to some alterations at the cervical and thoracic vertebral levels of the spinal cord or nerve roots. Maekawa, Hayase and Konishi attached importance to the presence of subclinical arachnoiditis adhesiva cerebrospinalis at the cervical and thoracic vertebral levels in patients of NCA. These facts suggests that the contribution of the spinal cord and the nerve roots to the circularoty system is different between the cervico-thoracic levels and the lumbar levels. Based on these facts, the author stimulated the somatic nerves of both the forelimbs and the hindlimbs afferently in alpha-chloralose anesthetized dogs, with a train of square electric pulses for 20 seconds, and studied the response of the circulatory system to such stimuli.     

A systematic review of neuroimaging data during visceral stimulation

OBJECTIVE: The application of functional imaging to study visceral sensation has generated considerable interest regarding insight into the function of the brain-gut axis, but also some contradictory and confusing results that require appraisal. METHODS: Published studies of visceral sensation were grouped according to stimulus region and study population. The results of each study were tabulated and the center of reported activations plotted onto the lateral and medial surface of a representative brain. RESULTS: Esophageal distension predominantly activated primary sensory and motor cortices and the midsection of the medial surface. Lower GI distension predominantly activated bilateral prefrontal and orbitofrontal cortices and more anterior and ventral regions of the medial surface. CONCLUSIONS: Activation sites are reasonably well clustered within stimulus modality, implying consistent brain response to visceral sensation. The differences in reported activation during esophageal and lower GI sensation imply altered motor, autonomic, and affect response during distension at opposite ends of the GI tract that may be explored in future studies.     

Evolving concepts in functional gastrointestinal disorders: promising directions for novel pharmaceutical treatments

In recent years there has been an increasing appreciation of the complexity of functional gastrointestinal disorders. These represent a spectrum of conditions which may affect any part of the gastrointestinal tract in which there appears to be dysregulation of visceral function and afferent sensation and a strong association with emotional factors and stress. There is a clear psychological dimension, with up to 60% of irritable bowel syndrome (IBS) patients reported to have psychological co-morbidities and altered pain perception is also common in comparison with control populations. The role of the enteric nervous system, the sensory pathways and the brain as well as the influence of the latter on sympathetic and parasympathetic outflow have likewise attracted increasing interest and have led to exciting new methods to study their complex interactions. The concept of low-grade inflammation, such as might occur after infection, acting as a trigger for neuromuscular dysfunction has also led to the broad integrative hypotheses that help to explain the biopsychosocial dimensions seen in functional gastrointestinal disease. The multi-component model places a major emphasis on neurogastroenterology and enteric and neuro-immune interactions where new approaches to pharmacotherapy lie. Drugs may affect motility, visceral sensation and other aspects of gut function such as secretion or absorption. More particularly, however, has been the search for and attempts to influence important mediators of these primary gut functions. Such targets include serotonin and selected 5-HT receptors, which are involved in gut motility, visceral sensation and other aspects of gut function, CCK receptors which are involved in the mediation of pain in the gut and nociception in the CNS, opioid receptors involved in pain in the brain, spinal cord and periphery, muscarinic M3-receptors, substance P and neurokinin A and B receptors which are involved in motor adaptation and pain transmission in association with inflammation, gabba receptors involved in nociception and cannabinoid receptors which are involved in the control of acetyl choline release in the gut. With a better understanding of the structures and pathways involved in visceral perception and hyperalgesia, in the CNS, spinal cord and the gut and new pharmacological tools we will be better able to elucidate the neuropharmacology of visceral perception and its relationship to gut dysfunction. It is likely that there will be multiple therapeutic options based on the spectrum of abnormalities capable of causing the spectrum of symptoms of functional gastrointestinal disorders in any individual patient.     

Motility disorders in the irritable bowel syndrome

Specific abnormalities of colonic and small bowel motility are identifiable and associated with symptoms in IBS. Characteristic abnormalities in colonic motility include a prolonged increase in 3-cycles/min colonic motor activity after a meal, an exaggerated increase in 3-cycles/min motor activity in response to stressors and CCK, and increased visceral sensitivity and motor activity in response to balloon distention. Symptoms in patients with IBS correlate in some cases with the abnormal gastrocolonic response and with pain induced by distention at various sites in the colon. Small bowel motility abnormalities identified reproducibly in IBS include an increase in daytime jejunal DCCs, an increase in daytime ileal PPCs, and more frequent cycling of daytime MMCs (in diarrhea-predominant IBS only). DCCs and PPCs are strongly associated with symptoms in IBS, and PPCs associated with altered ileocecal transit may be an important mechanism of symptoms in some patients with IBS. Esophageal and gastroduodenal motility abnormalities are inconsistently identified in IBS, and most symptoms in IBS appear to be secondary to small bowel or colonic dysfunction. Because of the paroxysmal nature of these motor abnormalities in IBS, prolonged motility recordings are required to better understand the pathophysiology of this syndrome. Patients with IBS may have altered visceral sensation and changes in afferent reflex mechanisms that modulate GI motility. These patients do not have a generalized increase in pain perception, but may have a distinct sensitivity to visceral afferent stimulation in both gastrointestinal and other viscera. Whether the altered "setpoint" to visceral afferent stimulation in IBS is intrinsic to the smooth muscle of viscera or secondary to CNS and ANS modulation is not known. Many of the symptoms and abnormalities of small bowel and colonic motility in IBS probably result from these changes in afferent sensation and reflex mechanisms. These findings support the concept that IBS is an abnormality of intestinal motility in conjunction with a "sensitive" gut.     

Role of neurokinin 3 receptors on responses to colorectal distention in the rat: electrophysiological and behavioral studies

BACKGROUND & AIMS: Tachykinins contribute to the control of gastrointestinal motility and modulation of somatic and visceral pain. The role of neurokinin (NK) B and NK3 receptors in visceral pain and gastrointestinal disorders has not been determined. METHODS: Using electromyographic recordings of both abdominal and colonic muscle and electrophysiological recordings of pelvic nerve afferent fibers, we studied drug effects on responses to colorectal distention. RESULTS: In awake rats, intraperitoneal administration of the NK3-receptor antagonist SR 142,801 reduced, whereas the NK3-receptor agonist senktide increased, both the rectocolonic inhibitory reflex and abdominal contractions produced by colorectal distention. In contrast, intracerebroventricular administration of SR 142,801 increased the number of abdominal contractions without affecting the rectocolonic inhibitory reflex produced by colorectal distention. In a similar manner, intracerebroventricular injection of senktide diminished the number of abdominal contractions. In electrophysiological experiments, SR 142,801 decreased responses of pelvic nerve afferent fibers to colorectal distention. Responses of pelvic nerve fibers to urinary bladder distention, however, were unaffected by SR 142,801. CONCLUSIONS: These results suggest that peripheral NK3 receptors are involved in the mediation of both visceral nociception and gastrointestinal disorders. Also, central NK3 receptors seem to play a role in the modulation of visceral nociception.     

From Cardiac Nociception to the Brain: The Unstable Character of Angina Pectoris

Sympathetic Afferents and Cardiac Pain. We analyzed some particular aspects of the peripheral pathways likely to be involved in the mediation of cardiac pain. The functional characteristics and the reflex function of cardiac sympathetic afferent fibers are discussed in relation to the afferent code transmitting nociception. A modified version of the intensity theory based on the extreme excitation of a spatially restricted population of afferent sympathetic fibers is proposed as the most likely mechanism involved in the genesis of cardiac pain.     

Traditional thoughts on the pathophysiology of irritable bowel syndrome

The pathogenesis of symptoms in irritable bowel syndrome (IBS) is multifactorial and varies from patient to patient. Disturbances of motor function in the small intestine and colon and smooth-muscle dysfunction in other gut and extraintestinal regions are prominent. Abnormalities of sensory function in visceral and somatic structures are detected in most patients with IBS, which may relate to peripheral sensitization or altered central nervous system processing of afferent information. Contributions from psychosocial disturbances are observed in patients from tertiary centers and primary practice. Proof of causation of symptom genesis for most of these factors is limited.     

Mechanosensitive N-methyl-D-aspartate receptors contribute to sensory activation in the rat renal pelvis

The N-methyl-D-aspartate (NMDA) subtype of the ionotropic glutamate receptor is found in the periphery. The present study tested whether NMDA receptors (NMDARs) are present in the ends of afferent renal nerves in the renal pelvis, an area concerned mainly with transmitting sensation and the to reflex regulation of body fluid. The main NMDAR subunit, NMDAzeta1, was found to be more abundant in the renal pelvis than the renal cortex and medulla, and was mainly colocalized with the pan-neuronal marker PGP9.5 or the sensory nerve marker, the neurokinin-1 receptor. However, NMDAzeta1 mRNA was undetectable, suggesting that it might be synthesized outside the renal pelvis. Intrarenal arterial administration of the specific ion channel blocker (+)-MK-801, but not the inactive enantiomer (-)-MK-801, decreased urine output and sodium excretion. High doses of (+)-MK-801 also caused regional vasoconstriction in the renal cortex, as determined by laser-Doppler flowmetry. Intrapelvic administration of the NMDAR ligand D-serine caused a dose-dependent increase in substance P (SP) release and afferent renal nerve activity, but had no effect on arterial pressure. The D-serine-induced sensory activation and SP release were abrogated by (+)-MK-801, the SP receptor blocker L-703,606, or dorsal rhizotomy. Increasing intrapelvic pressure resulted in an increase in afferent renal nerve activity and a diuretic/natriuretic response. Interestingly, these effects were attenuated by prior administration of (+)-MK-801. These results indicate that NMDAR-positive sensory nerves are present in the renal pelvis and contribute to the renorenal reflex control of body fluid.     

Cerebral cortical registration of subliminal visceral stimulation

BACKGROUND & AIMS: Although brain registration of subliminal somatic stimulations such as masked visual stimuli and their influence on electrical and hemodynamic measures of cerebral activity have been reported previously, there have been no reports on cerebral cortical registration of subliminal visceral stimulation. Because studies evaluating the consequences of subliminal somatic stimulation have shown that subliminal stimulation can effect behavior, it is conceivable that such subliminal messages from the intestine could potentially influence intestinal sensory/motor function or effect the perception/interpretation of sensory signals originating from the gut. METHODS: We studied the cerebral cortical functional magnetic resonance imaging (fMRI) response to subliminal, liminal, and supraliminal rectal distention in healthy volunteers. RESULTS: Study findings indicate that subliminal afferent signals originating from the gut are registered in the cerebral cortex without reaching the level of awareness. Locations of cortical activity caused by intestinal subliminal stimulation are similar to those of liminal and supraliminal stimulation but their intensity and volume are significantly lower (P < 0.05). CONCLUSIONS: Subliminal afferent signals originating from the gut are registered in the cerebral cortex and induce changes in measures of brain activity, such as hemodynamic changes detectable by fMRI.     

肾去神经治疗:How far have we got?

原发性高血压、胰岛素抵抗、充血性心力衰竭、慢性肾功能不全都存在中枢交感神经的过度激活,这种效应来源之一是由肾交感传入神经对中枢交感神经的激活。因此,识别肾交感神经对治疗以上疾病有着重要意义。交感神经系统的长期过度激活还与代谢综合征(如血压的升高、肥胖、血脂代谢紊乱、伴有高胰岛素血症的空腹血糖受损)相关。在此综述中,将说明选择性去除肾交感神经治疗难治性高血压不仅可以降低中枢交感神经的激活,还可影响一些有中枢交感神经过度激活的疾病,如胰岛素抵抗、充血性心力衰竭、利尿剂抵抗和心肾综合征等。